Lasli, Soufian; (2024) Tuneable hydrogel-based micropillar arrays for myelination studies. Doctoral thesis (Ph.D), UCL (University College London).

Text Soufian_PhD_thesis_final.pdf - Other Access restricted to UCL open access staff until 1 February 2026. Download (121MB)

Abstract

Myelin, a crucial component of the central nervous system (CNS), plays a pivotal role in facilitating efficient signal transmission along the axons of neurons. Oligodendrocytes (OLs) are the cells in the CNS producing myelin and extending their long processes around axons, which serve as an insulating sheath enabling efficient communication between neurons. Dysregulation or disruption of myelination can contribute to various neurological disorders such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease and more. Unfortunately, there are no currently approved therapies whose primary mechanism of action is to stimulate myelin repair. Understanding myelination is of great importance for unraveling the mechanisms underlying these neurological disorders in order to develop new therapies. This thesis presents the development of a novel platform aimed at visualising and studying the complex process of myelination in vitro. Cortical rat OLs were first cultured and characterised on 2D well plates. Different isolation techniques and media compositions were used and optimised to lead to healthy long-term cultures of highly pure OLs. It was found that the addition of growth factors into the medium and a recovery period is essential for healthy differentiation, maturation and survival of OLs. However, studying myelination is challenging using such 2D systems. With that aim, novel tuneable hydrogel-based micropillar arrays mimicking axons and around which OLs can grow and wrap around were developed. The micropillar characteristics can easily be manipulated allowing to dissect their effects on OL differentiation and myelination. The spatial configuration of arrays allows to image large fields of view with high resolution enabling high-throughput data acquisition. This platform is compatible with confocal microscopy, scanning and transmission electron microscopy (SEM, TEM) which are all essential in the characterisation of myelin. Clear compact and concentric multilayered myelin deposition around the pillars with a similar nanostructure to around neurons has been shown. This platform was used to study the effect of pillar geometry, ligand coating, stiffness and promyelinating compounds on OL myelination. Finally, it was demonstrated that the system is compatible with the culture of human OLs which were shown to differentiate and wrap around micropillars.

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